lncRNA PCAT1 might coordinate ZNF217 to promote CRC adhesion and invasion through regulating MTA2/MTA3/Snai1/E-cadherin signaling

Abstract

LncRNA prostate cancer-associated transcript 1 (PCAT1) is a well-known oncogene, but the mechanisms of exosomes PCAT1 in colorectal cancer (CRC) remain largely unknown. Thus, the mechanisms of exosomes lncRNA PCAT1 were investigated. The expressions of exosomes lncRNA PCAT1 in tissues from stage 0-I and stage II-III CRC patients, and intestinal epithelial cell line FHC and two CRC cell lines, HT29 and HCT8 were measured by real-time quantitative PCR. The effects of lncRNA PCAT1 on adhesion and invasion of two CRC cell lines were investigated by cell-matrix adhesion and transwell assays. In addition, the target of PCAT1 (ZNF217) was validated using an RNA immune precipitation assay. Finally, the protein levels of MTA2, MTA3, SNAI1, and E-cadherin in normal participants, stage 0-I and stage II-III CRC patients, as well as two cell lines with stable ZNF217 knockdown were investigated by western blotting. The plasma exosomal lncRNA PCAT1 was found to be significantly increased in the CRC tissues and cell lines. In addition, lncRNA PCAT1 knockdown significantly inhibited the adhesion and invasion of HT29 and HCT8 cells. RIP assay results showed lncRNA PCAT1 could target ZNF217, and downregulation of lncRNA PCAT1 could decrease the protein expressions of ZNF217 in two CRC cells lines. Moreover, ZNF217 knockdown significantly decreased MTA2, MTA3, and SNAI1 expressions, but increased E-cadherin expressions in both CRC cells lines. Exosomal lncRNA PCAT1 can promote the adhesion and invasion of CRC cells, and PCAT1 overexpression may lead to ZNF217 upregulation that regulates EMT-related MTA2/MTA3/Snai1/E-cadherin signaling

The role of zinc finger proteins in malignant tumors

“…Similarly, ZNF143 suppresses cell apoptosis and promotes proliferation in gastric cancer via ROS/p53 axis 59 . In accordance with these observations, ZNF217 may promote tumor progression by inducing cell migration and invasion in OVCA and CRC 76,101 . Considering the dysregulated expression of ZNFs in multiple cancer types, the possible explanation is an unknown factor that may interact with ZNFs in carcinogenesis.…”

“…These results demonstrate that miR193a‐5p‐mediated inhibition of ZNF746/c‐Myc signaling in Morusin induces apoptosis in CRCs 75 . LncRNA prostate cancer‐associated transcript 1 (PCAT1) increases ZNF217 expression to promote the adhesion and invasion of CRC through activating the EMT‐associated MTA2/MTA3/Snai1/E‐cadherin signaling pathway 76 …”

“…59 In accordance with these observations, ZNF217 may promote tumor progression by inducing cell migration and invasion in OVCA and CRC. 76,101 Considering the dysregulated expression of ZNFs in multiple cancer types, the possible explanation is an unknown factor that may interact with ZNFs in carcinogenesis. Therefore, additional experiments are needed to verify this hypothesis.…”

The Intricate Interplay between the ZNF217 Oncogene and Epigenetic Processes Shapes Tumor Progression

“…The lncRNA prostate-associated transcript 1 (PCAT1) is a well-known oncogene that was found to be upregulated in colorectal cancer tissues and exosomes derived from colorectal patients [ 85 ]. The same study identified that ZNF217 expression levels were negatively regulated by lncRNA PCAT1 silencing.…”

“…The same study identified that ZNF217 expression levels were negatively regulated by lncRNA PCAT1 silencing. The study suggested that lncRNA PCAT1 might co-ordinate ZNF217 to enhance colorectal cancer progression through the regulation of an EMT axis involving two metastasis-associated 1 family members (MTA2/MTA3) and Snai1/E-cadherin ( Figure 3 ) [ 85 ]. While the authors argue a putative physical interaction between lncRNA PCAT1 and ZNF217 , future work is further needed to confirm and to unravel the impact of any possible physical interaction between ZNF217 and any specific lncRNA.…”